Because renal cell carcinoma is notoriously resistant to chemotherapy and radiation, and only occasionally cured by surgery, a prospective randomized controlled chemotherapy trial was established to compare efficacy of PO CCNU, IV vinblastine, and IV Thiotepa. Patients failing to respond to first line therapy were then treated with IM bleomycin. 26 patients with metastatic renal cell carcinoma have been randomized between the three first line forms of therapy, and 7 patients had received bleomycin. The three method treatment groups are equivalent in age, therapy, time from diagnosis to therapy and incidences of CNS metastases. Nine patients were treated with CCNU and 7 were evaluable; there were no responses, 1 stabilization and 6 progressions of the disease. Ten patients received vinblastine with 2 objectives responses; one stabilization and 7 progressions. Seven patients received Thiotepa and there was 1 month partial remission, 1 stabilization and 5 progressions. of the 7 patients treated with bleomycin there were 2 stabilizations and 5 progressions. Mild-to-moderate myelosuppression was a major side effect for each drug regimen. Emesis occurred in only the CCNU group. Survival times were equivalent for all three primary forms of therapy and did not differ from historical controls. The protocol has been discontinued and a paper is being submitted for publication.